Microbiology and Immunology

Berg, Paul WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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an economically devastating disease that dwarfs tobacco

plants and mottles their leaves.

Beijerinck, who graduated from the Delft Polytechnic

School, began his research under the assumption that the

tobacco mosaic disease was caused by an unidentified bac-

terium or a parasite. Attempting to isolate the causative agent,

Beijerinck filtered the sap of an infected plant to remove all

known bacteria; however, the resulting liquid was still infec-

tive. In addition, the filtered substance was capable of infect-

ing another plant, which could infect another, demonstrating

that the substance had the ability to multiply and grow. The

Russian botanist Dmitri Ivanovsky had come up against the

same type of agent, but had failed to report its existence,

assuming instead that his research was flawed.

In 1898 Beijerinck published his work, which main-

tained that tobacco mosaic disease was caused not by bacteria,

but by a living liquid virus that infected only growing plant

organs where cellular division allowed it to multiply. This new

agent he called a filterable virus, from Latin meaning filterable

poison. Louis Pasteurhad speculated about the existence of

germs that were smaller than bacteria, but did not conduct

research into this phenomenon. Beijerinck asserted that the

virus was liquid, but this theory was later disproved by

Wendell Stanley, who demonstrated the particulate nature of

viruses. Beijerinck, nevertheless, set the stage for twentieth-

century virologists to uncover the secrets of viral pathogens

now known to cause a wide range of plant and animal (includ-

ing human) diseases.

See alsoVirology; Virus replication; Viruses and responses to

viral infection

BBerg, Paul ERG, PAUL(1926- )

American biochemist

Paul Berg developed a technique for splicing together

(DNA)—the substance that carries genetic information in liv-

ing cells from generation to generation—from different types

of organisms. Berg’s achievement, one of the most fundamen-

tal technical contributions to the field of genetics in the twen-

tieth century, gave scientists an invaluable tool for studying

the structure of viral chromosomesand the biochemical basis

of human genetic diseases. It also allowed researchers to turn

simple organisms into chemical factories that churn out valu-

able medical drugs. In 1980 Berg was awarded the Nobel

Prize in chemistry for pioneering this procedure, now referred

to as recombinant DNAtechnology.

The commercial application of Berg’s work underlies a

large and growing industry dedicated to manufacturing drugs

and other chemicals. Moreover, the ability to recombine

pieces of DNA and transfer them into cells is the basis of an

important new medical approach to treating diseases by a

technique called genetherapy.

Berg was born in Brooklyn, New York, one of three

sons of Harry Berg, a clothing manufacturer, and Sarah

Brodsky, a homemaker. He attended public schools, including

Abraham Lincoln High School, from which he graduated in

1943. In a 1980 interview reported in the New York Times,
      Berg credited a “Mrs. Wolf,” the woman who ran a science
      club after school, with inspiring him to become a researcher.
      He graduated from high school with a keen interest in micro-
      biology and entered Pennsylvania State University, where he
      received a degree in biochemistryin 1948.
      Before entering graduate school, Berg served in the
      United States Navy from 1943 to 1946. On September 13,
      1947, he married Mildred Levy; the couple later had one son.
      After completing his duty in the navy, Berg continued his study
      of biochemistry at Western Reserve University (now Case
      Western Reserve University) in Cleveland, Ohio, where he was
      a National Institutes of Health fellow from 1950 to 1952 and
      received his doctorate degree in 1952. He did postdoctoral
      training as an American Cancer Society research fellow, work-
      ing with Herman Kalckar at the Institute of Cytophysiology in
      Copenhagen, Denmark, from 1952 to 1953. From 1953 to 1954
      he worked with biochemist Arthur Kornberg at Washington
      University in St. Louis, Missouri, and held the position of
      scholar in cancer research from 1954 to 1957.
      He became an assistant professor of microbiology at the
      University of Washington School of Medicine in 1956, where
      he taught and did research until 1959. Berg left St. Louis that
      year to accept the position of professor of biochemistry at
      Stanford University School of Medicine. Berg’s background
      in biochemistry and microbiology shaped his research inter-
      ests during graduate school and beyond, steering him first into
      studies of the molecular mechanisms underlying intracellular
      protein synthesis.
      During the 1950s, Berg tackled the problem of how
      amino acids, the building blocks of proteins, are linked
      together according to the template carried by a form of RNA
      (ribonucleic acid, the “decoded” form of DNA) called mes-
      senger RNA (mRNA). A current theory, unknown to Berg at
      the time, held that the amino acids did not directly interact
      with RNA but were linked together in a chain by special mol-
      ecules called joiners, or adapters. In 1956 Berg demonstrated
      just such a molecule, which was specific to the amino acid
      methionine. Each amino acid has its own such joiners, which
      are now called transfer RNA (tRNA).
      This discovery helped to stoke Berg’s interest in the
      structure and function of genes, and fueled his ambition to
      combine genetic material from different species in order to
      study how these individual units of heredity worked. Berg rea-
      soned that by recombining a gene from one species with the
      genes of another, he would be able to isolate and study the
      transferred gene in the absence of confounding interactions
      with its natural, neighboring genes in the original organism.
      In the late 1960s, while at Stanford, Berg began study-
      ing genes of the monkey tumor virus SV40 as a model for
      understanding how mammalian genes work. By the 1970s, he
      had mapped out where on the DNA the various viral genes
      occurred, identified the specific sequences of nucleotides in
      the genes, and discovered how the SV40 genes affect the DNA
      of host organisms they infect. It was this work with SV40
      genes that led directly to the development of recombinant
      DNA technology. While studying how genes controlled the
      production of specific proteins, Berg also was trying to under-

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